Prospective validation and clinical evaluation of a new posaconazole dosing regimen for children and adolescents with cystic fibrosis and Aspergillus infection.

Prospective validation and clinical evaluation of a new posaconazole dosing regimen for children and adolescents with cystic fibrosis and Aspergillus infection. - cASPerCF

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-004511-31-PT

Enrollment

135

Registered

2021-01-18

Start date

2021-06-18

Completion date

Unknown

Last updated

2024-07-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis and Aspergillus infection. MedDRA version: 20.0 Level: LLT Classification code 10003488 Term: Aspergillosis System Organ Class: 100000004862

Interventions

Trade Name: NOXAFIL - oral suspension 40 mg/ml Product Name: Noxafil Pharmaceutical Form: Oral suspension Trade Name: Noxafil 100 mg Product Name: Noxafil Pharmaceutical Form: Gastro-resistant table

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Inclusion criteria for the screening phase: 1. Diagnosed with cystic fibrosis (genetic diagnosis and/or abnormal sweat test and clinical phenotype of lung disease) 2. Age = 8 yrs and =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: Exclusion criteria for the screening phase: 1. Non-CF lung disorder 2. Age < 8 yrs of age or =18 yrs of age 3. Body weight < 20 kg 4. Not able to provide sputum sample 5. Informed Consent not given Exclusion criteria for the intervention phase: 1. Non-CF lung disorder 2. Age < 8 yrs or =18 yrs 3. Body weight < 20 kg 4. Not able to perform lung function test (FEV1%) 5. Unable to produce a sputum sample (spontaneous or induced sputum) 6. Clinically unstable condition with significant change in lung function or significant worsening of respiratory symptoms 7. Unable to tolerate oral medication 8. Known hypersensitivity to itraconazole or posaconazole, or it’s excipients. 9. On active transplant list or transplant recipient 10. Azole resistant Aspergillus sp. Cultured 11. Patients receiving terfenadine, ergot alkaloids, astemizole, cisapride, pimozide, halofantrine, quinidine, or HMG-CoA reductase inhibitors metabolised through CYP3A4 (eg. simvastatin, lovastatin, and atorvastatin) 12. Patients receiving omalizumab 13. Received systemic mould-active antifungals in the last month 14. Shortened or elongated QT interval 15. Cardiac failure 16. ALT = 200 U/L 17. AST = 225 U/L 18. Alkaline phosphatase = 460 U/L 19. Bilirubin = 50 umol/L 20. eGFR = 20 ml/min/1.73 m2 (calculated with the Schwartz formula) 21. Patients with known glucose-galactose malabsorption problems 22. Pregnancy2 or breastfeeding 23. Females of childbearing age who do not intend to use contraception measures. 24. Informed Consent not given

Design outcomes

Primary

Measure	Time frame
Main Objective: PK - To validate a paediatric posaconazole dosing regimen for children and adolescents with CF and Aspergillus infection. Clinical efficacy: - To examine the efficacy of posaconazole versus usual care in children and adolescents with CF and Aspergillus infection in terms of clearance of Aspergillus from the airways after three months;Secondary Objective: PK - To define in silico the optimal dose for patients with CF aged 8 - 17 years. - To define the optimal detailed dosepharmacokinetics in a limited number of children and adolescents with CF and Aspergillus infection aged 8-17 yrs through an intensive PK sampling study Epidemiology, Clinical efficacy and safety: - To determine the prevalence of Aspergillus infection in children and adolescents aged 8 to 17 years. - To assess the safety and tolerability of posaconazole in children and adolescents with CF and Aspergillus infection. - To Assess the clinical efficacy of posaconazole versus usual care in terms of (1) serological responses to clearance of Aspergillus from the airways; (2) dampening airway inflammation, and (3) clinical outcomes (as measured by pulmonary exacerbation rate, days on antibiotics and corticosteroids, hospital admissions, quality of life, change in FEV1, change in BMI, CT- chest abnormalities);Primary end point(s): - For the dosing algorithm: The number of children and adolescents with CF and Aspergillus infection aged 8 to 17 years reaching the pre-defined area under the concentration time curve (AUC) of posaconazole at the first assessment (between day 5 and 10) based on the adult reference concentrations for treatment of susceptible pathogens. - For clinical efficacy: The number of children with negative sputum sample for Aspergillus infection at 3 months. ;Timepoint(s) of evaluation of this end point: - For the dosing algorithm: between day 5 and 10 - For clinical efficacy: 3 months.	—

Measure

Time frame

Main Objective: PK - To validate a paediatric posaconazole dosing regimen for children and adolescents with CF and Aspergillus infection. Clinical efficacy: - To examine the efficacy of posaconazole versus usual care in children and adolescents with CF and Aspergillus infection in terms of clearance of Aspergillus from the airways after three months;Secondary Objective: PK - To define in silico the optimal dose for patients with CF aged 8 - 17 years. - To define the optimal detailed dosepharmacokinetics in a limited number of children and adolescents with CF and Aspergillus infection aged 8-17 yrs through an intensive PK sampling study Epidemiology, Clinical efficacy and safety: - To determine the prevalence of Aspergillus infection in children and adolescents aged 8 to 17 years. - To assess the safety and tolerability of posaconazole in children and adolescents with CF and Aspergillus infection. - To Assess the clinical efficacy of posaconazole versus usual care in terms of (1) serological responses to clearance of Aspergillus from the airways; (2) dampening airway inflammation, and (3) clinical outcomes (as measured by pulmonary exacerbation rate, days on antibiotics and corticosteroids, hospital admissions, quality of life, change in FEV1, change in BMI, CT- chest abnormalities);Primary end point(s): - For the dosing algorithm: The number of children and adolescents with CF and Aspergillus infection aged 8 to 17 years reaching the pre-defined area under the concentration time curve (AUC) of posaconazole at the first assessment (between day 5 and 10) based on the adult reference concentrations for treatment of susceptible pathogens. - For clinical efficacy: The number of children with negative sputum sample for Aspergillus infection at 3 months. ;Timepoint(s) of evaluation of this end point: - For the dosing algorithm: between day 5 and 10 - For clinical efficacy: 3 months.

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Secondary

Measure	Time frame
Secondary end point(s): PK -The number of children and adolescents with CF and Aspergillus infection aged 8 to 17 years reaching the pre-defined area under the concentration time curve (AUC) of posaconazole at the second and third assessment (day 21-35, EOT) based on the adult reference concentrations for treatment of susceptible pathogens. Epidemiology, Clinical efficacy and safety - The proportion of children and adolescents aged 8 to 17 years with CF who screened positive for Aspergillus infection - The proportion of participants experiencing AEs and SAEs - Dose-response relationships between posaconazole exposure and toxicity - Forced expiratory volume (FEV1) at 3, 6 and 12 months post randomisation to evaluate if posaconazole is beneficial for CF-related Aspergillus infection. - Aspergillus in the airways (positive sputum culture) 3, 6 and 12 months post randomisation to evaluate if posaconazole is able to clear CF-related Aspergillus infection. - Levels of Aspergillus specific IgG and IgE 3, 6 and 12 months post randomisation to evaluate if posaconazole is able to normalize those levels. - Airway inflammation as measured by proteome profiling of sputum at baseline and 3 months post randomisation to evaluate if posaconazole is able to dampen inflammation in CF-related Aspergillus infection. - Clinical disease severity (as measured by pulmonary exacerbation rate, days on antibiotics and corticosteroids, hospital admissions, change in FEV1, change in BMI, CT-chest abnormalities) 3, 6 and 12 months post randomisation to evaluate if posaconazole has a beneficial effect. - Patient reported outcomes 3, 6 and 12 months post randomisation to evaluate if posaconazole has a beneficial effect (validated CFQR).;Timepoint(s) of evaluation of this end point: -Day 21-35 -3, 6 and 12 months post randomisation	—

Measure

Time frame

Secondary end point(s): PK -The number of children and adolescents with CF and Aspergillus infection aged 8 to 17 years reaching the pre-defined area under the concentration time curve (AUC) of posaconazole at the second and third assessment (day 21-35, EOT) based on the adult reference concentrations for treatment of susceptible pathogens. Epidemiology, Clinical efficacy and safety - The proportion of children and adolescents aged 8 to 17 years with CF who screened positive for Aspergillus infection - The proportion of participants experiencing AEs and SAEs - Dose-response relationships between posaconazole exposure and toxicity - Forced expiratory volume (FEV1) at 3, 6 and 12 months post randomisation to evaluate if posaconazole is beneficial for CF-related Aspergillus infection. - Aspergillus in the airways (positive sputum culture) 3, 6 and 12 months post randomisation to evaluate if posaconazole is able to clear CF-related Aspergillus infection. - Levels of Aspergillus specific IgG and IgE 3, 6 and 12 months post randomisation to evaluate if posaconazole is able to normalize those levels. - Airway inflammation as measured by proteome profiling of sputum at baseline and 3 months post randomisation to evaluate if posaconazole is able to dampen inflammation in CF-related Aspergillus infection. - Clinical disease severity (as measured by pulmonary exacerbation rate, days on antibiotics and corticosteroids, hospital admissions, change in FEV1, change in BMI, CT-chest abnormalities) 3, 6 and 12 months post randomisation to evaluate if posaconazole has a beneficial effect. - Patient reported outcomes 3, 6 and 12 months post randomisation to evaluate if posaconazole has a beneficial effect (validated CFQR).;Timepoint(s) of evaluation of this end point: -Day 21-35 -3, 6 and 12 months post randomisation

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Countries

Czechia, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Sweden, Switzerland, United Kingdom

Contacts

Public ContactA.R. INFETTIVOLOGIA E SVILUPPO DI F

Bambino Gesù Children's Hospital

betty.polikar@opbg.net

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026